CPLM 1.0 - Compendium of Protein Lysine Modification
TagContent
CPLM ID CPLM-012711
UniProt Accession
Genbank Protein ID
Genbank Nucleotide ID
Protein Name
 Hypoxia-inducible factor 1-alpha 
Protein Synonyms/Alias
 HIF-1-alpha; HIF1-alpha; ARNT-interacting protein; Basic-helix-loop-helix-PAS protein MOP1; Class E basic helix-loop-helix protein 78; bHLHe78; Member of PAS protein 1; PAS domain-containing protein 8 
Gene Name
 HIF1A 
Gene Synonyms/Alias
 BHLHE78; MOP1; PASD8 
Created Date
 July 27, 2013 
Organism
 Homo sapiens (Human) 
NCBI Taxa ID
 9606 
Lysine Modification
Position
Peptide
Type
References
32AARSRRSKESEVFYEubiquitination[1]
56NVSSHLDKASVMRLTubiquitination[1]
71ISYLRVRKLLDAGDLubiquitination[1]
185RGRTMNIKSATWKVLubiquitination[1]
251SRHSLDMKFSYCDERubiquitination[1]
289LDSDHLTKTHHDMFTubiquitination[1]
297THHDMFTKGQVTTGQubiquitination[1]
377KMTQLFTKVESEDTSubiquitination[1]
389DTSSLFDKLKKEPDAubiquitination[1]
477LNQEVALKLEPNPESubiquitination[1]
538FKLELVEKLFAEDTEubiquitination[1]
709PEEELNPKILALQNAubiquitination[1]
Reference
 [1] Landscape of the PARKIN-dependent ubiquitylome in response to mitochondrial depolarization.
 Sarraf SA, Raman M, Guarani-Pereira V, Sowa ME, Huttlin EL, Gygi SP, Harper JW.
 Nature. 2013 Apr 18;496(7445):372-6. [PMID: 23503661] 
Functional Description
 Functions as a master transcriptional regulator of the adaptive response to hypoxia. Under hypoxic conditions, activates the transcription of over 40 genes, including erythropoietin, glucose transporters, glycolytic enzymes, vascular endothelial growth factor, HILPDA, and other genes whose protein products increase oxygen delivery or facilitate metabolic adaptation to hypoxia. Plays an essential role in embryonic vascularization, tumor angiogenesis and pathophysiology of ischemic disease. Binds to core DNA sequence 5'-[AG]CGTG-3' within the hypoxia response element (HRE) of target gene promoters. Activation requires recruitment of transcriptional coactivators such as CREBPB and EP300. Activity is enhanced by interaction with both, NCOA1 or NCOA2. Interaction with redox regulatory protein APEX seems to activate CTAD and potentiates activation by NCOA1 and CREBBP. Involved in the axonal distribution and transport of mitochondria in neurons during hypoxia. 
Sequence Annotation
 DOMAIN 17 70 bHLH.
 DOMAIN 85 158 PAS 1.
 DOMAIN 228 298 PAS 2.
 DOMAIN 302 345 PAC.
 REGION 1 401 Interaction with TSGA10 (By similarity).
 REGION 380 417 N-terminal VHL recognition site.
 REGION 401 603 ODD.
 REGION 531 575 NTAD.
 REGION 556 572 C-terminal VHL recognition site.
 REGION 576 785 ID.
 REGION 786 826 CTAD.
 MOTIF 718 721 Nuclear localization signal (Potential).
 MOD_RES 247 247 Phosphoserine; by CK1.
 MOD_RES 402 402 4-hydroxyproline.
 MOD_RES 551 551 Phosphoserine; by GSK3-beta.
 MOD_RES 555 555 Phosphothreonine; by GSK3-beta.
 MOD_RES 564 564 4-hydroxyproline.
 MOD_RES 576 576 Phosphoserine; by PLK3.
 MOD_RES 589 589 Phosphoserine; by GSK3-beta.
 MOD_RES 657 657 Phosphoserine; by PLK3.
 MOD_RES 800 800 S-nitrosocysteine (Probable).
 MOD_RES 803 803 (3S)-3-hydroxyasparagine.
 CROSSLNK 391 391 Glycyl lysine isopeptide (Lys-Gly)
 CROSSLNK 477 477 Glycyl lysine isopeptide (Lys-Gly)
 CROSSLNK 532 532 Glycyl lysine isopeptide (Lys-Gly)
 CROSSLNK 538 538 Glycyl lysine isopeptide (Lys-Gly)
 CROSSLNK 547 547 Glycyl lysine isopeptide (Lys-Gly)  
Keyword
 3D-structure; Activator; Alternative splicing; Complete proteome; Cytoplasm; Direct protein sequencing; DNA-binding; Hydroxylation; Isopeptide bond; Nucleus; Phosphoprotein; Polymorphism; Reference proteome; Repeat; S-nitrosylation; Transcription; Transcription regulation; Ubl conjugation. 
Sequence Source
 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 
Protein Length
 826 AA 
Protein Sequence
MEGAGGANDK KKISSERRKE KSRDAARSRR SKESEVFYEL AHQLPLPHNV SSHLDKASVM 60
RLTISYLRVR KLLDAGDLDI EDDMKAQMNC FYLKALDGFV MVLTDDGDMI YISDNVNKYM 120
GLTQFELTGH SVFDFTHPCD HEEMREMLTH RNGLVKKGKE QNTQRSFFLR MKCTLTSRGR 180
TMNIKSATWK VLHCTGHIHV YDTNSNQPQC GYKKPPMTCL VLICEPIPHP SNIEIPLDSK 240
TFLSRHSLDM KFSYCDERIT ELMGYEPEEL LGRSIYEYYH ALDSDHLTKT HHDMFTKGQV 300
TTGQYRMLAK RGGYVWVETQ ATVIYNTKNS QPQCIVCVNY VVSGIIQHDL IFSLQQTECV 360
LKPVESSDMK MTQLFTKVES EDTSSLFDKL KKEPDALTLL APAAGDTIIS LDFGSNDTET 420
DDQQLEEVPL YNDVMLPSPN EKLQNINLAM SPLPTAETPK PLRSSADPAL NQEVALKLEP 480
NPESLELSFT MPQIQDQTPS PSDGSTRQSS PEPNSPSEYC FYVDSDMVNE FKLELVEKLF 540
AEDTEAKNPF STQDTDLDLE MLAPYIPMDD DFQLRSFDQL SPLESSSASP ESASPQSTVT 600
VFQQTQIQEP TANATTTTAT TDELKTVTKD RMEDIKILIA SPSPTHIHKE TTSATSSPYR 660
DTQSRTASPN RAGKGVIEQT EKSHPRSPNV LSVALSQRTT VPEEELNPKI LALQNAQRKR 720
KMEHDGSLFQ AVGII 735 
Gene Ontology
 GO:0005829; C:cytosol; TAS:Reactome.
 GO:0005730; C:nucleolus; IDA:HPA.
 GO:0005667; C:transcription factor complex; IPI:MGI.
 GO:0051879; F:Hsp90 protein binding; IDA:BHF-UCL.
 GO:0000988; F:protein binding transcription factor activity; IDA:BHF-UCL.
 GO:0046982; F:protein heterodimerization activity; TAS:UniProtKB.
 GO:0001077; F:RNA polymerase II core promoter proximal region sequence-specific DNA binding transcription factor activity involved in positive regulation of transcription; IEA:Compara.
 GO:0003705; F:RNA polymerase II distal enhancer sequence-specific DNA binding transcription factor activity; IDA:BHF-UCL.
 GO:0043565; F:sequence-specific DNA binding; IEA:Compara.
 GO:0004871; F:signal transducer activity; IEA:InterPro.
 GO:0044212; F:transcription regulatory region DNA binding; IDA:UniProtKB.
 GO:0001525; P:angiogenesis; IEA:Compara.
 GO:0019896; P:axon transport of mitochondrion; IMP:UniProtKB.
 GO:0001922; P:B-1 B cell homeostasis; IEA:Compara.
 GO:0003208; P:cardiac ventricle morphogenesis; IEA:Compara.
 GO:0051216; P:cartilage development; IEA:Compara.
 GO:0006879; P:cellular iron ion homeostasis; IEA:Compara.
 GO:0071347; P:cellular response to interleukin-1; IEP:BHF-UCL.
 GO:0021987; P:cerebral cortex development; IEA:Compara.
 GO:0032963; P:collagen metabolic process; ISS:BHF-UCL.
 GO:0002248; P:connective tissue replacement involved in inflammatory response wound healing; ISS:BHF-UCL.
 GO:0048546; P:digestive tract morphogenesis; IEA:Compara.
 GO:0071542; P:dopaminergic neuron differentiation; IEA:Compara.
 GO:0051541; P:elastin metabolic process; ISS:BHF-UCL.
 GO:0035162; P:embryonic hemopoiesis; IEA:Compara.
 GO:0001892; P:embryonic placenta development; IEA:Compara.
 GO:0061030; P:epithelial cell differentiation involved in mammary gland alveolus development; IEA:Compara.
 GO:0001837; P:epithelial to mesenchymal transition; ISS:BHF-UCL.
 GO:0042593; P:glucose homeostasis; IEA:Compara.
 GO:0001947; P:heart looping; IEA:Compara.
 GO:0042541; P:hemoglobin biosynthetic process; IEA:Compara.
 GO:0060574; P:intestinal epithelial cell maturation; IEA:Compara.
 GO:0006089; P:lactate metabolic process; IEA:Compara.
 GO:0007595; P:lactation; IEA:Compara.
 GO:0042789; P:mRNA transcription from RNA polymerase II promoter; IC:BHF-UCL.
 GO:0046716; P:muscle cell homeostasis; IEA:Compara.
 GO:0030502; P:negative regulation of bone mineralization; IEA:Compara.
 GO:0045926; P:negative regulation of growth; IEA:Compara.
 GO:2001054; P:negative regulation of mesenchymal cell apoptotic process; IEA:Compara.
 GO:0043524; P:negative regulation of neuron apoptotic process; IEA:Compara.
 GO:0032007; P:negative regulation of TOR signaling cascade; IEA:Compara.
 GO:0001755; P:neural crest cell migration; IEA:Compara.
 GO:0021502; P:neural fold elevation formation; IEA:Compara.
 GO:0007219; P:Notch signaling pathway; TAS:Reactome.
 GO:0003151; P:outflow tract morphogenesis; IEA:Compara.
 GO:0032364; P:oxygen homeostasis; IDA:HGNC.
 GO:0045766; P:positive regulation of angiogenesis; IC:BHF-UCL.
 GO:0032722; P:positive regulation of chemokine production; TAS:BHF-UCL.
 GO:0070101; P:positive regulation of chemokine-mediated signaling pathway; IC:BHF-UCL.
 GO:0001938; P:positive regulation of endothelial cell proliferation; IC:BHF-UCL.
 GO:0010634; P:positive regulation of epithelial cell migration; ISS:BHF-UCL.
 GO:0045648; P:positive regulation of erythrocyte differentiation; IC:BHF-UCL.
 GO:0045821; P:positive regulation of glycolysis; IC:BHF-UCL.
 GO:0046886; P:positive regulation of hormone biosynthetic process; IDA:BHF-UCL.
 GO:0035774; P:positive regulation of insulin secretion involved in cellular response to glucose stimulus; IEA:Compara.
 GO:0002052; P:positive regulation of neuroblast proliferation; IEA:Compara.
 GO:0051000; P:positive regulation of nitric-oxide synthase activity; TAS:BHF-UCL.
 GO:0010870; P:positive regulation of receptor biosynthetic process; IMP:BHF-UCL.
 GO:0061419; P:positive regulation of transcription from RNA polymerase II promoter in response to hypoxia; IDA:BHF-UCL.
 GO:0030949; P:positive regulation of vascular endothelial growth factor receptor signaling pathway; IC:BHF-UCL.
 GO:0010575; P:positive regulation vascular endothelial growth factor production; IDA:BHF-UCL.
 GO:0043619; P:regulation of transcription from RNA polymerase II promoter in response to oxidative stress; IDA:BHF-UCL.
 GO:0032909; P:regulation of transforming growth factor beta2 production; IMP:BHF-UCL.
 GO:0014850; P:response to muscle activity; IEA:Compara.
 GO:0061298; P:retina vasculature development in camera-type eye; IEA:Compara.
 GO:0010573; P:vascular endothelial growth factor production; IDA:BHF-UCL.
 GO:0008542; P:visual learning; IEA:Compara. 
Interpro
 IPR011598; bHLH_dom.
 IPR001321; HIF-1_alpha.
 IPR014887; HIF-1_TAD_C.
 IPR021537; HIF_alpha_subunit.
 IPR001610; PAC.
 IPR000014; PAS.
 IPR013767; PAS_fold.
 IPR013655; PAS_fold_3. 
Pfam
 PF11413; HIF-1
 PF08778; HIF-1a_CTAD
 PF00989; PAS
 PF08447; PAS_3 
SMART
 SM00353; HLH
 SM00086; PAC
 SM00091; PAS 
PROSITE
 PS50888; BHLH
 PS50113; PAC
 PS50112; PAS 
PRINTS
 PR01080; HYPOXIAIF1A.